With the increasingly aging population,osteoporosis morbidity had been gradually increased and the incidence of the hips and vertebral fractures showed a trend of rapid growth,which brought great pain and economic burden to patients and society.There were a variety of anti-osteoporosis drugs clinically,which interfere with the development of osteoporosis via multi-approaches to reduce the clinical symptoms and improve their quality of life.In this paper,the author aimed to make a review of the research progress of anti-osteoporosis drug clinical application.

Objective To investigate effects of physical exercise (PE) on object recognition memory in adult rats of postnatal isoflurane (Iso) exposures.Methods One hundred and ten postnatal 7-day SD rats (P7) were randomly divided into four groups: normal control group (Naive), Naive+PE group (received physical exercise in P21: a treadmill exercise 30min each day, 5 times/week, for 6 weeks), Iso group (three times of 2-hour Iso exposure in P7, P9, and P11), and Iso+PE group (received PE in P21 after postnatal Iso exposures). In P67, behavioral testing was conducted including open field and object recognition task (ORT), recording the time (Discrimination Ratios, DR) that rats spent on exploring each object, evaluating effects of PE on object recognition memory.Results There was no significant difference in influence of PE on open field testing in all of the groups (P>0.05). Compared with Naive, there was no group difference in DR (P>0.05) for all groups, but the DR of Iso male rats was significantly higher than that of Naive female rats in P67, with significant difference (P=0.034). Compared with non-PE groups, whether or not postnatal Iso exposures, the DR of PE male groups was significantly higher (compared with Naive and Iso group:P67,P=0.050,P=0.017; P95,P=0.037,P=0.019); in female rats, the DR for ISO+PE group was lower than that of Iso group in P67 (P=0.036), but the DR of Naive+PE group was higher than that of Naive group in P95 (P=0.004). Compared with male rats, the DR of non-PE female rats was significantly higher in P67 (vis. Naive and Iso group:P=0.022,P=0.011); but in P95, the DR of non-Iso female groups was significantly higher than that of male groups (vis. Naive and Naive+PE:P=0.008,P=0.017).Conclusions There is no obvious impact of postnatal Iso exposures on object recognition memory of adult rats. These Results also indicate that postnatal PE could improve object recognition memory of non-spatial learning in adult rats. In addition, exercise benefits have gender differences.

Objective To investigate effects of isoflurane anesthesia of different time interval on acute injury of brain function in neonatal rats with consistent total time of isoflurane anesthesia. Methods Seven-day neonatal Sprague-Dawley (SD) rats were randomly divided into normal control group (breathe the air), continuous anesthesia group (a single 6-hour exposure to 1.5% isoflurane), and intermittent anesthesia 1 day and 3 days groups (three times of 2-hour exposure to anesthesia with an interval of 1 day or 3 days), 12 rats in each group. The ratio of male to female was 5:7. They underwent the test of learning and memory in the radial arm maze (RAM) 21 days after birth, twice a day for 4 days. The number of entry into wrong arms, number of repeated errors, number of total arm entries, and time for completing the task were recorded for evaluation of effect of neonatal isoflurane on cognitive behavior in rats. Results ① Compared with normal control group, the percentage of number of errors > 3 in anesthesia of 3-day interval group was significantly decreased (33.3% vs. 46.9%, P < 0.05), the percentages of repeated errors > 0 and total arm entries > 8 were significantly increased (33.3% vs. 18.8%, 27.1% vs. 13.5%, both P < 0.05), but there were no statistically significant difference in the percentage of mistake number > 3 between continuous anesthesia group, interval anesthesia 1-day group and the normal control group (44.8%, 44.8% vs. 46.9%), the percentages of number of repeated mistake > 0 and total arm entries > 8 in above three groups were slightly increased as compared with those of normal control group (27.1%, 22.9% vs. 18.8%, 20.8%, 21.9% vs. 13.5%, all P > 0.05). No statistical differences in completing the task among normal control group, continuous anesthesia group, interval anesthesia 1 day and 3 days groups were found (minutes: 1.32±0.91, 1.54±1.05, 1.46±0.86, 1.38±0.79, all P > 0.05). ② It was found by gender analysis that the percentages number of repeated errors > 0 and total arm entries > 8 were significantly lower in female rats than those in the male rats only in normal control group (5.0% vs. 28.6%, P < 0.01; 5.0% vs. 19.6%, P < 0.05). There was no obvious gender difference in exposed groups. ③ Compared between groups of female rats, the percentages of repeated mistake > 0 in continuous anesthesia group, interval anesthesia 1 day and 3 days groups (25.0%, 25.0%, 30.0% vs. 5.0%, P < 0.05 or P < 0.01) and the percentage of total arm entries > 8 in interval anesthesia 1 day and 3 days groups were significantly higher than that of normal control group (22.5%, 25.0% vs. 5.0%, both P < 0.05). No significant difference about the RAM task in male rats of all the four groups was found. Conclusions Different time interval of neonatal isoflurane exposure may develop certain degree of acute brain injury in rats, characterized by cognitive function. Prolongation of the interval time significantly enhanced long-term memory in rats. Multiple neonatal exposures to isoflurane were associated with greater cognitive impairment than a single exposure. In addition, isoflurane can significantly increase cognitional functional disorder in the female, not in the male rats.

BACKGROUND: With the development of tissue engineering, materials science, and biomechanics, developing new biodegradable ureteral stent has become an issue of concern. The ureteral stent with poly(L-lactide-co-ε-caprolactone)/crosslinked polypyrrolidone was prepared. OBJECTIVE: To explore the histocompatibility of the ureteral stent grafted into the bladder of Sprague-Dawley rats. METHODS: Sixty male Sprague-Dawley rats (provided by Laboratory Animal Center of Sichuan Academy of Traditional Chinese Medicine) were randomly divided into four groups, each group containing 15 rats. The sham operation group was directly sutured after opening a small incision on the outside of the bladder, and no material was implanted. The other three groups were implanted with polyurethane ureteral stent (control group), poly(L-lactide-co-ε-caprolactone)/8% cross-linked polyvinylpyrrolidone ureter stent (experiment group 1), poly(L-lactide ε- caprolactone)/5% cross-linked polyvinylpyrrolidone ureteral stent (experiment group 2) after opening a small incision on the outer side of the bladder, followed by suturing the incision. At 4, 8, and 16 weeks after operation, the local anatomy of the bladder was observed. The histocompatibility of the materials in each group was observed by hematoxylin-eosin staining. The study was approved by the Ethical Committee of Laboratory Animal Analysis and Testing Center of West China School of Public Health, Sichuan University. RESULTS AND CONCLUSION: (1) Gross observation: At 4, 8 and 16 weeks postoperatively, different degrees of chronic inflammation reaction occurred in the control group and experimental group 1. In the experiment group 2, chronic inflammatory reaction appeared at 4 weeks postoperatively. The stone formation rate in the control group and experimental group 1 was significantly higher than that in the sham operation group (P < 0. 05) at 4 and 16 weeks postoperatively, which showed no significant difference at 8 weeks postoperatively among groups (P > 0. 05). The calculus formation rate in the experimental group 2 was significantly higher than that in the sham operation group only at 4 weeks postoperatively, and had no significant difference at other time points (P > 0. 05). (2) Pathological observation: Different degrees of foreign body in the outer membrane, inflammatory reaction and diffuse hyperplasia of the mucosa were found in the control group, experimental groups 1 and 2 at different time points postoperatively. There was no significant difference in the rate of diffuse hyperplasia of the mucosa at different time points postoperatively among groups (P > 0. 05), but higher than that in the sham operation group (P < 0. 05). (3) These results indicate that the calculus formation rate and bladder histological reaction of poly(L-lactide-co-ε-caprolactone)/cross-linked polyvinylpyrrolidone ureter stent are comparable with those of commercial ureteral stents, especially the addition of 5% cross-linked polyvinylpyrrolidone has better histocompatibility.

Objective:To investigate the vasorelaxant effect of the isoflavones in red clover on rat mesenteric artery rings. Meth-ods:The rat mesenteric artery rings were placed between two L form metal needles. When stable precontractions induced by vasocon-strictor were got, the different concentrations of isoflavones in red clover and ( or) blocker were added to the baths. The isometric ten-sion of the rat mesenteric artery rings was recorded using a myograph system. Results:The isoflavones in red clover could concentra-tion-dependently relax the rat mesenteric artery rings pre-contracted by K+krebs solution (60 mmol·L-1K+), and compared with the control group (Dmso), the difference was statistically significant (P<0. 01). The isoflavones in red clover-induced relaxation was re-duced by the removal of endothelium, and compared with the complete endothelial group, the difference was statistically significant ( P<0. 01). Pretreatment with Nω-nitro-L-arginine-methylesterhydrochloride (L-NAME,10 -4 mol·L-1) could suppress the relaxing re-sponse to the isoflavones in red clover, and compared with the control group, the difference was statistically significant (P<0. 01). However, indomethacin(10 -5 mol·L-1) did not significantly affect the relaxation induced by the isoflavones in red clover (P >0. 05). Conclusion:The vasorelaxant effect of the isoflavones in red clover is through promoting nitric oxide release from vascular en-dothelium.

Objective:To investigate the vasorelaxant effect of the isoflavones in red clover on rat mesenteric artery rings. Meth-ods:The rat mesenteric artery rings were placed between two L form metal needles. When stable precontractions induced by vasocon-strictor were got, the different concentrations of isoflavones in red clover and ( or) blocker were added to the baths. The isometric ten-sion of the rat mesenteric artery rings was recorded using a myograph system. Results:The isoflavones in red clover could concentra-tion-dependently relax the rat mesenteric artery rings pre-contracted by K+krebs solution (60 mmol·L-1K+), and compared with the control group (Dmso), the difference was statistically significant (P<0. 01). The isoflavones in red clover-induced relaxation was re-duced by the removal of endothelium, and compared with the complete endothelial group, the difference was statistically significant ( P<0. 01). Pretreatment with Nω-nitro-L-arginine-methylesterhydrochloride (L-NAME,10 -4 mol·L-1) could suppress the relaxing re-sponse to the isoflavones in red clover, and compared with the control group, the difference was statistically significant (P<0. 01). However, indomethacin(10 -5 mol·L-1) did not significantly affect the relaxation induced by the isoflavones in red clover (P >0. 05). Conclusion:The vasorelaxant effect of the isoflavones in red clover is through promoting nitric oxide release from vascular en-dothelium.

A large number of medical studies have confirmed that inflammation with occurrence and de-velopment of tumor are closely related. In recent years,it has been confirmed and described that the tumor-relat-ed inflammatory response plays an important role in the prognosis of tumor. Furthermore,the tumor-related in-flammatory response can be reflected by the patient′s neutrophils,lymphocytes,monocytes and other peripheral blood indicators,such as peripheral blood lymphocytes and mononuclear cells ratio( LMR) . LMR plays an impor-tant role in the diagnosis and prognosis of tumor patients. In many studies from China and other countries,LMR has been described digestive,blood and other systems of malignant tumors,which it plays an important role in the prognosis. There is little domestic and foreign report on the research progress of LMR on the gynecological repro-ductive system. Therefore,this article reviews the effect of LMR on the prognosis of common gynecological malig-nancies.

Objective To study the immune intervention effect and mechanism of blockage of macrophage-mediated PD1 /PD-L1 pathways with functional PD-L1(programmed cell death ligand-1,PD-L1)monoclonal antibody upon tuberculosis(TB)relapse in mice. Methods Female C57BL/6 mice were infected by tail vein injection of 106CFU M. tuberculosis H37Rv to obtain active TB infection. Two weeks postinfection, the mice in different groups were administered isoniazid(10 mg/kg)(group ISO)and isoniazid combined with PD-L1 monoclonal antibody(50 μg/each)(group ISO+PD-L1)respectively,continued for four weeks to obtain latent infection. The subsequent relapse was monitored. Among the treatment groups,the TB relapse was induced by TNF-α antibody(50 ug/each)for four weeks from the beginning of latent stage. At each scheduled time point, bacterial loads and pathological changes in the lung, spleen and liver were quantitatively analyzed,thereby,the in vivo intervention effect of PD-L1 monoclonal antibody on tuberculosis recurrence in mice was revealed. The in vitro experiment was further explored whether knock-down the expression of PD-L1 on the infected macrophages could accerlate the macrophage apoptosis. Results The bacterial burden reached 3-4 Lg(CFU/mL),and granuloma lesions were extensive in the lung, spleen and liver in the all infected groups, which appeared as active TB stage at 2nd week postinfection. After treated,the bacterial burden of the lung,spleen and liver was decreased, and the pathological lesions alleviated in the group ISO and group ISO+PD-L1, compared with the model control group, showing significant differences, but there was no significant difference between the two treatment groups. However, compared with the group ISO,the group ISO+PD-L1 had a significantly lower bacterial load and milder pathological lesions during the relapse period. Futhermore, knock-down the expression of PD-L1 on macrophages with anti-PD-L1 or PD-L1-siRNA promoted apoptosis in macrophages. Conclusions Blockade of the PD1/PD-L1 pathway by PD-L1 functional antibody can inhibit TB relapse in mice,and knock-down the expression of PD-L1 on macrophages or PD1/PD-L1 pathway with functional antibody can promote apoptosis in macrophages,which together indicate that PD-L1 blockage can effectively promote isoniazid treatment of TB and remarkably inhibit the recurrence of TB in mice.

Objective TNF-α monoclonal antibody drugs are widely used to treat conditions such as rheumatic arthritis and ankylosing spondylitis. On the other hand, it is also a wide concern that the application of these drugs may increase the susceptibility of patients to infections such as tuberculosis and listeriosis. The aim of this study was to establish a mouse model of Listeria monocytogenes infection and to evaluate the effect of TNF-α monoclonal antibody on the host susceptibility to this infection. Methods Six SPF 14-week old female C57BL/6 mice and 12 SPF 14-week old female TNF-α humanized mice were injected with saline or adalimumab intravenously, and challenged with intraperitoneal injection of 104 CFU Listeria monocytogenes 24 h later. After one day or 4 days, the mice were sacrificed to examine the pathological lesions and the bacterial load in the spleen and liver. Results Four days after infection, the area of microabscess in the liver tissues was significantly increased in the adalimumab-treated group. The bacterial load in the spleen and liver tissues of the adalimumab-treated group was significantly higher than that of the C57BL/6 mouse control group and TNF-α humanized mouse control group (P ＜ 0. 05). However, the distribution of macrophages in the liver tissues and B cells in the spleen tissues were similar among groups. Conclusions TNF-α plays an important role in the host immune responses to Listeria monocytogenes infection. After the intervention with TNF-α monoclonal antibody, the progress of host disease is significantly exacerbated.

The implantation of interspinous process device is a minimal invasive surgical procedure for degenerative lumbar spinal diseases. At present, a variety of interspinous process devices designed can be subdivided into three categories based on different application principles: interspinous distraction device, interspinous fixation device and interspinous fusion device. The interspinous distraction devices distract interspinous interspace, enlarge spinal canal area and alleviate neurological symptom, which are mainly applied for lumbar spinal stenosis with intermittent neurogenic claudication. Interspinous fixation device has been used as an alternative technique to the pedicle screw fixation in lumbar interbody fusion due to gripping and fixating to spinous process. Interspinous fusion device utilizes rigid fixation to support fusion, which can be used as not only simple distraction device but also additional instrumentation for direct decompression and interbody fusion. All types of interspinous process devices are different in biomechanical characteristics due to its application concept. In this review, the author mainly focus on biomechanical research progress of interspinous process device in lumbar degenerative disease.